Effect of transforming growth factor-beta 1 on oestrogen metabolism in MCF-7 and MDA-MB-231 breast cancer cell lines

Transforming growth factor-beta (TGF-beta) has been shown to inhibit the gr owth of mammary epithelial cells and map play a protective role in mammary carcinogenesis. In contrast, oestrogens promote the development of breast c ancer. Oestrone sulphate (E1S) is a huge reservoir of active oestrogens in the breast being converted to the weak oestrogen, oestrone (E-1), by oestro ne sulphatase. E-1 is reversibly converted by oestradiol-17 beta hydroxyste roid dehydrogenase to the potent oestrogen, oestradiol (E-2). The aim of th is study was to assess the effect of the TGF-beta 1 isoform on growth and o estrogen metabolism in the hormone-dependent MCF-7 and hormone-independent MDA-MB-231 human breast cancer cell lines. The results showed that TGF-beta 1 significantly inhibited cell growth and stimulated the conversion of E1S to E-1 and E-1 to E-2 in the MCF-7 cell line. In the MDA-MB-231 cell line TGF-beta 1 significantly stimulated cell growth and inhibited the interconv ersions between E-1 and E-2. In conclusion, the growth inhibitory effect of TGF-beta 1 on the MCF-7 cell line would appear to confer a protective effe ct in breast cancer. However, its ability to increase the amount of E-2 wou ld increase the risk of breast cancer. Which of these effects predominates in vivo remains to be explored. The growth stimulatory effect of TGF-beta 1 on the MDA-MB-231 cell line probably acts through a mechanism independent of the effect of TGF-beta 1 on oestrogen concentrations since this cell lin e is hormone unresponsive.